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July 8, 2004

Research Notes

Grants awarded to researchers

The National Science Foundation has awarded a new grant of $388,851 to Mark Abbott of the School of Arts and Sciences’ geology and planetary science department for his study, “Hydrologic Bariability in the Pacific Northwest During the Past 13,000 Years From High Resolution Studies of Finely Laminated Lake Sediments.” The research has two goals: producing high resolution multiproxy records documenting changes in effective moisture and temperature for the last 13,000 years from lakes with annual layers, and determining the relationships between climatic change, aquatic nutrient cycling and productivity.

Michael Barmada of the Graduate School of Public Health (GSPH)’s human genetics department has received a new grant of $458,124 from the National Center for Research Resources to create a shared computational resource comprised of 200 processors running the Linux operating system and a storage system with -2 Tb of disk space. Initially, the major user group will be investigators with primary and secondary appointments in the human genetics department.

The National Institute of Allergy and Infectious Diseases has awarded a $487,541 continuation grant to Joanne Flynn of the School of Medicine’s molecular genetics and biochemistry department for research on CD4 T cells, which represent a crucial component of the protective immune response to tuberculosis.

The Office of Child Development’s Robert B. McCall has received a $599,166 continuation grant from the National Institute of Child Health and Human Development for research on the effects of improved caregiving on early mental health. The project is intended to improve the stability and consistency of caregiving staff and to train them to be more socially responsive and developmentally appropriate in a St. Petersburg, Russia, home for children aged 4 and younger, and to observe the consequences of such improved caregiving on early mental health of those children from the home who are adopted into the United States.

The National Heart, Lung and Blood Institute has awarded a $325,628 continuation grant to Michael Sacks of the School of Engineering’s bioengineering program for research on the biomechanical optimization of heart valves created through tissue engineering. Using autologous cells and biodegradable polymers, TE heart valves have functioned in the pulmonary circulation of growing lambs for up to four months.

Koichi Takimoto of GSPH’s environmental and occupational health department has received a new grant of $302,255 from the National Heart, Lung and Blood Institute for a study, “Regulation of KV Channels by Anorexigens.”

The University of Pittsburgh Cancer Institute’s Chandra Belani has been awarded a new grant of $252,000 from Eli Lilly and Co. for “A Phase I and Pharmacokinetic Study of Gemcitabine in Combination with Oxaliplatin and Capecitabine in Advanced Solid Tumors.” The study is aimed at determining the maximum tolerated dose of each drug when used in combination and the toxicities association with this regimen.

The U.S. Department of Education has granted $888,141 to Gina Bertocci of the School of Health and Rehabilitation Sciences to continue funding the Rehabilitation Engineering Research Center on Wheelchair Transportation Safety.

Jes K. Klarlund of the School of Medicine’s ophthalmology department has received a $379,242 continuation grant from the National Eye Institute for research on “Corneal Innervation and Epithelial Cell Migration.”

The Freeman Foundation has awarded a new grant of $432,028 to Bell Yung of the University Center for International Studies for an initiative to promote greater understanding among undergraduates of Asia in a global and comparative perspective.

The National Institute of Arthritis and Muscoloskeletal and Skin Diseases has awarded a new grant of $556,074 to Joseph Zmuda of GSPH’s epidemiology department for a study of bone loss among men of African heritage in Tobago. Although osteoporosis is more common in women, men also incur substantial bone loss with aging and approximately one-third of all hip fractures occur in men. In contrast to scientists’ understanding of the etiology and prevention of osteoporosis in women, considerably less is known of the determinants of skeletal health in men, especially non-whites.

Research challenges link between depression, dementia

Older people who become depressed are prone to developing dementia, two to four years later. However, new research from Pitt shows that half of depressed elderly patients have significant cognitive problems at the time they are depressed, but the other half do not.

The study, published in the June edition of the Archives of General Psychiatry, builds on results that author Meryl Butters, assistant professor of psychiatry at Pitt’s School of Medicine, and her colleagues published four years ago, showing that even after successful depression treatment, elderly patients with depression did not regain the level of cognition they had before they became depressed.

“This should be a wake-up call to doctors that when a depressed elderly patient shows up at the office complaining of memory problems, they need to treat the depression and the cognitive problems as two separate disorders,” Butters said.

“We realized the cause of these cognitive impairments was due to some other disease process going on under the surface,” she said. “In this study we took a closer look at the link between cognitive problems and depression and found it is not as strong as previously thought. Being depressed itself does not cause cognitive impairments. If significant cognitive problems exist in an elderly depressed person, they are likely permanent and may worsen over time.”

The study of 140 depressed patients 60 years and older is the most comprehensive study to date of the range, type and depth of cognitive impairments in depressed seniors.

The research was supported by U.S. Public Health Service grants. Pitt School of Medicine researchers at Western Psychiatric Institute and Clinic recently began a follow-up study to determine what treatments work best to treat depression and either restore or halt cognitive decline in elderly patients. For more information about that study, please call 412/246-6006.

Advances have led to better management of sports-related hip injuries

Advances in diagnostic imaging, arthroscopic surgery techniques and neuromuscular research have given both the recreational and elite athlete a much better chance for a quicker, safer return to activity following a hip injury that previously may have gone unrecognized and untreated.

The latest advances in managing sports-related hip injuries were presented in four separate talks by a team of University of Pittsburgh Medical Center (UPMC) sports medicine researchers and clinicians at this year’s annual meeting of the National Athletic Trainers Association (NATA) June 14-19 in Baltimore. The UPMC presentations served as the meeting’s annual Johnson & Johnson Keynote Symposium, sponsored by Johnson & Johnson Consumer Products, Inc.

Various factors involved in the cause, prevention, treatment and rehabilitation of sports-related hip instability and injury have become significantly more recognized and manageable during the past few years as a result of intensive ongoing laboratory and clinical research at the UPMC Center for Sports Medicine.

Four internationally recognized sports-related hip injury experts from UPMC who presented the keynote symposium were: Marc Philippon, who discussed emerging trends in hip arthroscopy; Scott Lephart, who demonstrated neuromuscular considerations for hip joint instability; Pete Draovitch, who discussed rehabilitation options and outcomes, and Bryan Kelly, who reviewed the pathoetiology of labral tears.

Lephart, director of the UPMC Center for Sports Medicine’s Neuromuscular Research Laboratory, has led numerous studies involving both recreational and high-level athletes – including professional golfers, hockey, football and baseball players – who must use constant high-profile hip rotation in their sport, making them more prone to joint wear-and-tear injury and chronic instability.

Lephart’s ongoing research has revealed important factors of neuromuscular control, stability, balance, strength and flexibility of the hip that is leading to the development of effective conditioning programs for preventing, treating and rehabilitating from hip injury.

Meanwhile, Philippon, one of the world’s leading arthroscopic hip surgeons and director of sports-related hip injury services at UPMC, has been perfecting a surgical technique that he has performed successfully on hundreds of elite and professional athletes with hip joint instability, returning them to their high level of performance. The injury type has become more commonly recognized in high-performance athletes who must use constant hip rotation in their sport. Previously, the injury was difficult to diagnose and was often misdiagnosed as lower back or groin injuries, thus treated ineffectively. Thanks to advanced diagnostic magnetic resonance imaging, the injury has become recognized as joint cartilage looseness and labral tears that can be repaired with special flexible arthroscopic instruments that Philippon developed specifically to treat this injury. The minimally invasive surgical repair technique allows for a quicker return to high level performance.

Philippon’s most recent famous patients have included Philadelphia Flyer goalies Robert Esche and Sean Burke, Maple Leafs right winger Tie Domi, Kansas City Chiefs running back Priest Holmes, and Pittsburgh Steelers place kicker Jeff Reed.

Lephart and Philippon’s teams collaborate on research and clinical services with world-renowned UPMC physical therapy and rehabilitation specialist Pete Draovitch, who also is a certified athletic trainer and certified strength and conditioning specialist. Draovitch’s patients have included numerous professional golfers such as Greg Norman, who has participated in some of the UPMC research projects.

UPMC center analyzes where biodefense dollars have gone

Since 9/11 and the subsequent anthrax attacks, the U.S. government has spent substantial resources on preparing the nation against a bioterrorist attack. To date, however, there has not been a clear accounting for, and analysis of, how civilian biodefense funding has been allocated and spent.

The Center for Biosecurity of the University of Pittsburgh Medical Center has released a summary and analysis of government spending over the past four years, as well as spending levels projected for 2005. The article appears in the June 2004 issue of Biosecurity and Bioterrorism at

The article analyzes the civilian biodefense funding by the federal government from fiscal years 2001 through 2005, specifically analyzing the budgets and allocations for biodefense at the Department of Health and Human Services, the Department of Homeland Security, the Department of Defense, the Department of Agriculture, the Environmental Protection Agency, the National Science Foundation, and the Department of State. Among the findings:

• The U.S. government has spent approximately $14.5 billion on civilian biodefense in FY2001 through FY2004, with another $7.6 billion in the president’s budget request for FY2005.

• The two agencies primarily responsible for civilian biodefense – the Department of Health and Human Services (DHHS) and the Department of Homeland Security (DHS) – together account for more than 90 percent of budgeted civilian biodefense funds.

• Although DHHS received a steep increase in funding in FY2002, funding has essentially remained at the same level since FY2003.

• One-third of the money allocated to DHS for FY2004 is for Project BioShield. In FY2005, BioShield will comprise 85 percent of DHS’s civilian biodefense funding. According to Ari Schuler, research analyst at the center and author of the article, funding has grown for most agencies since 2001 but some agencies are now seeing their funding level off or, in some cases, decrease.

“This report is the first comprehensive accounting of post-September 11th biodefense spending by the U.S. government,” Schuler said. “The next step is for the government and independent groups to begin comprehensively analyzing the programs that have been funded by this $15 billion effort.”

“Billions for Biodefense: Federal Agency Biodefense Funding, FY2001-FY2005” appears in Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science, published by Mary Ann Liebert, Inc., and available at

Researchers to test treatment for Alzheimer’s

The Alzheimer’s Disease Research Center (ADRC) at Pitt has been chosen as a research site to participate in the first human clinical trials of an investigational treatment for Alzheimer’s disease.

The investigational drug known as AAB-001, a specific antibody to beta-amyloid, is thought to work by removing a protein called beta-amyloid, which is present only in small amounts in the normal brain but is greatly increased in the brains of Alzheimer’s patients.

Researchers believe the amyloid plaques result from unknown genetic and environmental miscues that cause the brain to produce and deposit it in clumps. The accumulation of amyloid plaque is believed to cause the death of neurons, in part by stimulating another abnormal protein metabolism known as neurofibriallary tangles in neurons, resulting in memory loss. As the disease progresses, more and more plaques accumulate and patients suffer greater cognitive impairments.

“Working with AAB-001 gives us an exciting opportunity to continue our Alzheimer’s disease research,” said Steven T. DeKosky, professor of neurology, psychiatry, neurobiology and human genetics at Pitt’s School of Medicine and director of the ADRC. “If the safety data from these initial clinical tests are positive, larger clinical trials may be initiated to determine whether AAB-001 can be a potential treatment breakthrough.”

The drug, AAB-001, is the first of its kind to emerge for testing since trials of an anti-amyloid vaccine were suspended two years ago due to medical complications. AAB-001 is a novel monoclonal antibody, using synthetically engineered antibodies directed to seek out and reduce amyloid. The monoclonal antibody is intended to provide the patient’s immune system with the capability to respond to the amyloid, a key difference from the earlier vaccine strategy. In that study, the vaccine, AN-1792, stimulated the patient to mount their own immune response, that is, produce their own antibodies.

The primary purpose of this study is to evaluate the safety of AAB-001 and how well increasing doses of AAB-001 (in successive groups of subjects) are tolerated. A secondary purpose of the study is to measure the amount of AAB-001 in the blood, and how long it remains in the blood over time.

AAB-001 is an investigational drug and is not currently approved for commercial use by the U.S. Food and Drug Administration. In this study, AAB-001 is being given to humans for the first time. The study is sponsored by Wyeth Research, and is an initiative of the Elan/Wyeth Alzheimer’s Immunotherapy Program.

The study has so far enrolled three patients in Pittsburgh and will eventually include approximately eight. Participants must meet criteria outlined in the study protocol.

Finn receives NCI, Dana Foundation grants

The National Cancer Institute has awarded a five-year, $6.9 million grant to the Department of Immunology’s Olivera J. Finn and collaborators for the continuing program project, “Dendritic Cell Biology and Therapy.” This program project brought dendritic cell-related research to Pitt, and helped to make Pittsburgh one of the world’s leading centers in research on dendritic cell biology and therapy.

Even though the major focus of the program is on the immune responses to cancer, it provides a forum for exchange of ideas and experiences between highly acclaimed experts not only in cancer, but also in diabetes, transplantation and asthma.

Finn also has received a three-year, $300,000 Dana Foundation Human Immunology Grant Competitive Invitational Research Program award for a consortium project, “Immune Markers of Premalignant Disease,” a collaborative program between scientists at Pitt’s School of Medicine and the Rockefeller University.

The study will focus on two groups of patients:

• Patients with monoclonal gammopathy of undetermined significance as a premalignant precursor of hematological tumors, and

• Long-term smokers with premalignant lung lesions, precursors of lung adenocarcinomas.

The $300,000 granted to Finn represents Pitt’s portion of the award.

Chemist recognized for macromolecule research

Christian E. Schafmeister, assistant professor in Pitt’s Department of Chemistry, has been awarded a $1.4 million grant from the National Institutes of Health and has received a $616,000 National Science Foundation (NSF) Faculty Early Career Development Award.

Schafmeister also was named a Research Corporation Cottrell Scholar, which comes with a $75,000 grant. These honors recognize Schafmeister’s innovative approach to synthesizing molecular building blocks, which can be snapped together to form large molecules.

While chemists today can synthesize almost any small- and medium-sized molecule, it takes years of effort to synthesize large molecules. Large molecules are interesting because they can do things that small molecules cannot. The best example of this is biological proteins such as enzymes, the large molecules that carry out many of the processes of life. Enzymes, which are proteins large enough to contain pockets for enveloping other smaller molecules, speed biological processes by modifying smaller molecules.

Schafmeister’s research group synthesizes small, rigid molecular building blocks called bis-amino acids and couples them through pairs of bonds called amide bonds to create complex, three-dimensional structures. The building blocks can be combined to have an enormous variety of three-dimensional structures, including those that contain pockets that can bind small molecules and sense or operate on them. “It will be very valuable to be able to synthesize large molecules that have designed shapes because we could construct shapes that carry out valuable new functions,” said Schafmeister.

In nature, single amino acids are attached to one another and form long chains, and then fold into complex three-dimensional shapes. Little is understood about how amino acids chains know the correct way to fold themselves to make a functional protein. “Predicting how a protein folds is like tossing a rope into the air and predicting what shape it will assume when it hits the ground. In our approach, we build rigid molecules that resemble twisted ladders and are inherently rigid, and so we don’t have to worry about folding,” said Schafmeister.

The group is working to develop fluorescent sensors and other molecular devices using this new technology.

Schafmeister will use part of the NSF and Cottrell funding to create software for use in organic chemistry classrooms. He is developing software that displays and manipulates molecule models in three-dimensions for use in chemistry lecture halls equipped with stereo projectors.

“One of the greatest difficulties that undergraduate students have in learning organic chemistry is in visualizing the three-dimensional nature of molecules based on their two dimensional representations,” said Schafmeister. “Stereo projection equipment has recently become affordable enough to permit its installation in lecture halls, but the content and software is almost nonexistent.”

Sponsored by Research Corporation, the Cottrell Scholar Award recognizes beginning faculty in the sciences who excel in teaching and research. The award commemorates Frederick Gardner Cottrell, founder of Research Corporation, chemist, and inventor of the Cottrell electrostatic precipitator.

NSF Faculty Early Career Development Awards are made to junior-level university faculty to emphasize the importance NSF places on integrating research and education activities in academic careers.

Biodefense grants awarded to researcher

Saleem Khan of the School of Medicine’s molecular genetics and biochemistry department has received two grants totaling more than $1 million from the National Institute of Allergy and Infectious Diseases under the Biodefense and Emerging Infectious Diseases Research Opportunities Program. One study deals with “Plasmid pXO2 Replication in Bacillus anthracis” while the other research involves “Genomics/Proteomics of Enterotoxin B Producing S. aureus”.

Pitt among institutions awarded $4.2 million for gynecologic cancer program

At a June 29 press conference at Windber Research Institute, Congressman John P. Murtha (D-Johnstown) announced funding for a major initiative to foster new understanding of gynecologic cancers that are newly diagnosed in approximately 80,000 women each year – 27,000 of whom are expected to die of their disease.

Murtha obtained $4.2 million from the U.S. Department of Defense for the initiative, a collaboration among the University of Pittsburgh Cancer Institute (UPCI), the Windber Research Institute (WRI), Walter Reed Army Medical Center and Georgetown University to create a program solely dedicated to reducing the incidence, morbidity and mortality of gynecologic cancers. Murtha said, “This program represents an important step in our effort to make significant advances in women’s health – in this case, the prevention and treatment of gynecologic cancers and other debilitating diseases that have a tremendous impact on women.”

“The key to cures, or at least long-term survival from cancer, lies in our ability to detect it early, before symptoms have appeared and before the cancer has spread,” said UPCI director Ronald B. Herberman. “Thanks to the support of Congressman Murtha, we now have the opportunity and tools to work collectively to improve our ability to detect gynecologic cancers and make a true impact on morbidity and mortality rates from these diseases.”

The initiative will focus on characterizing the molecular alterations associated with benign and malignant gynecologic diseases and facilitate the development of novel early detection, prevention and treatment strategies for the management of gynecologic cancers such as ovarian, cervical and endometrial, as well as non-cancerous gynecologic diseases such as uterine fibroids and endometriosis.

The five aims of the program are to improve the ability to detect gynecologic diseases earlier, develop molecular profiling technologies, determine the influence of hormones on cancer risk, identify the molecular expression patterns associated with disease, and develop new therapies for gynecologic tumors. To achieve the objectives of the partnership, the organizations will utilize tissue banking, epidemiologic data collection, clinical research and basic science research.

Ophthalmology receives grants

The UPMC Eye Center of the Pitt School of Medicine’s ophthalmology department has received two awards from Research to Prevent Blindness (RPB), the world’s leading voluntary organization supporting eye research. To date, the organization has awarded grants totaling $2,239,175 to Pitt’s medical school.

RPB awarded a grant of $110,000 to the ophthalmology department to support research into the causes, treatments and prevention of blinding diseases. The research will be directed by Joel S. Schuman, Eye and Ear Foundation Professor and chairperson of the ophthalmology department.

The second award is a two-year extension of the Jules & Doris Stein RPB Professorship. The professorship was first awarded to the medical school’s James L. Funderburgh in 1999. In total, the Jules & Doris Stein RPB Professorship will provide $625,000 in support over seven years. Funderburgh’s lab conducts research on corneal cell biology and tissue engineering and is focusing on the development of an artificial cornea.

“UPMC Eye Center is thankful for the support we receive from Research to Prevent Blindness,” said Schuman. “The philanthropy shown by this organization, as well as that received by the Eye and Ear Foundation and University of Pittsburgh School of Medicine from individuals and other charitable organizations, allows us to perform ground breaking work in battling blindness.”

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